Summary of Work: We have elucidated a novel signaling pathway linking pertussis toxin sensitive G proteins to potassium channel stimulation through ser/thr directed protein phosphatases, which are the molecular target of a growing list of potent and widespread environmental toxins. We showed previously that this pathway involves arachidonic acid metabolites, and identified a lipid-stimulated ser/thr protein phosphatase, PP5. We have cloned PP5 from rat pituitary tumor cells and obtained direct molecular evidence for its involvement in potassium channel stimulation by somatostatin receptors in those cells. We have investigated the contribution of the phosphatase to other endpoints of somatostatin action on cell physiology, and we have begun to characterize the variation in the effectiveness of somatostatin signaling with cell cycle, growth factor exposure and substratum adhesion which might contribute to individual susceptibility to the toxins that disrupt this pathway.